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Enhanced cardiac function in transgenic mice expressing a Ca(2+)-stimulated adenylyl cyclase.

Publication ,  Journal Article
Lipskaia, L; Defer, N; Esposito, G; Hajar, I; Garel, MC; Rockman, HA; Hanoune, J
Published in: Circ Res
April 14, 2000

The predominant functional adenylyl cyclases normally expressed in cardiac tissue and coupled to beta-adrenergic receptors are inhibited by micromolar Ca(2+) concentration. To modify the overall balance of activities, we have generated transgenic mice expressing the Ca(2+)-stimulatable adenylyl cyclase type 8 (AC8) specifically in the heart. AC activity is increased by at least 7-fold in heart membranes from transgenic animals and is stimulated by Ca(2+) in the same range of concentration that inhibits the endogenous activity. Moreover, the in vivo basal protein kinase A activity was augmented 4-fold. Overexpression of AC8 in the heart has no detrimental consequences on global cardiac function. Basal heart rate and contractile function, measured by noninvasive echocardiography, were unchanged. In contrast, on release of parasympathetic tone, the intrinsic contractility is heightened and unresponsive to further beta-adrenergic receptor stimulation. AC8 transgenic mice thus represent an original model to investigate the relative influence of Ca(2+) and cAMP on cardiac function within a phenotype of enhanced cardiac contractility and relaxation.

Duke Scholars

Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

April 14, 2000

Volume

86

Issue

7

Start / End Page

795 / 801

Location

United States

Related Subject Headings

  • Systole
  • Restriction Mapping
  • Receptors, Adrenergic, beta
  • Myocardium
  • Myocardial Contraction
  • Mice, Transgenic
  • Mice
  • Kinetics
  • Isoproterenol
  • Humans
 

Citation

APA
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ICMJE
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Lipskaia, L., Defer, N., Esposito, G., Hajar, I., Garel, M. C., Rockman, H. A., & Hanoune, J. (2000). Enhanced cardiac function in transgenic mice expressing a Ca(2+)-stimulated adenylyl cyclase. Circ Res, 86(7), 795–801. https://doi.org/10.1161/01.res.86.7.795
Lipskaia, L., N. Defer, G. Esposito, I. Hajar, M. C. Garel, H. A. Rockman, and J. Hanoune. “Enhanced cardiac function in transgenic mice expressing a Ca(2+)-stimulated adenylyl cyclase.Circ Res 86, no. 7 (April 14, 2000): 795–801. https://doi.org/10.1161/01.res.86.7.795.
Lipskaia L, Defer N, Esposito G, Hajar I, Garel MC, Rockman HA, et al. Enhanced cardiac function in transgenic mice expressing a Ca(2+)-stimulated adenylyl cyclase. Circ Res. 2000 Apr 14;86(7):795–801.
Lipskaia, L., et al. “Enhanced cardiac function in transgenic mice expressing a Ca(2+)-stimulated adenylyl cyclase.Circ Res, vol. 86, no. 7, Apr. 2000, pp. 795–801. Pubmed, doi:10.1161/01.res.86.7.795.
Lipskaia L, Defer N, Esposito G, Hajar I, Garel MC, Rockman HA, Hanoune J. Enhanced cardiac function in transgenic mice expressing a Ca(2+)-stimulated adenylyl cyclase. Circ Res. 2000 Apr 14;86(7):795–801.

Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

April 14, 2000

Volume

86

Issue

7

Start / End Page

795 / 801

Location

United States

Related Subject Headings

  • Systole
  • Restriction Mapping
  • Receptors, Adrenergic, beta
  • Myocardium
  • Myocardial Contraction
  • Mice, Transgenic
  • Mice
  • Kinetics
  • Isoproterenol
  • Humans